1. Field of the Invention
The invention relates to polyester copolymers, and more particularly to a bioresorbable aliphatic polyester copolymer with superior mechanical properties and modifiable decomposition period.
2. Description of the Related Art
Recently, with increased maturity of polymer technologies, polymer applications are involved in not only traditional plastics and synthetic resin industries but also high technology industries such as livelihood, and biotechnology. Some relative polymer materials with specific properties are critical for the related industries. For example, bioresorbable polymer, particularly those that include synthetic polymers or a combination of synthetic and naturally occurring polymers, have been used in a variety of medical and environmental protection applications.
Naturally occurring bioresorbable polymers include polypeptides (such as collagen and gelatin), polyamino acids (such as poly-L-glutamic acid and poly-L-lysine) and polysaccharides (such as hyaluronic acid, alginic acid, chitin, and chitosan). Naturally occurring bioresorbable polymers, however, have poor mechanical properties and are difficult to process and mass-produce.
Accordingly, attention has turned to synthetic polymers. Bioresorbable synthetic polymers commonly and currently used include polycaprolactone (PCL), polylatic acid (PLA), polyglycolic acid (PGA), poly lactide-co-glycolide (PLGA)), polyvinyl alcohol (PVA), polyhydroxy butyrate (PHB), polyanhydride, and polyortho ester. Since the aforementioned synthetic polymers mostly comprise a hydrolysable functional group, such as the ester group, the polymers hydrolyze gradually, and are thereby suitable for wide use in medical and environmental protection applications.
In some clinical conditions, implant fixation devices or materials are employed to fix soft or hard tissues. The fixation devices or materials must be removed from the host by a second procedure to avoid rejection, if they cannot biodegrade or be bioresorbed. The second procedure, however, is not only intrusive but also increases risk of infection and complications. Thus, bioresorbable fixation devices or materials have been widely developed and used in medical applications.
Smith et al. in U.S. Pat. No. 4,080,318 disclose a polycaprolactone urethane derivative, comprising the reaction product of polycaprolactone polyol and polycarboxylic acid anhydride via copolymerization, wherein the polycaprolactone polyol has a molecular weight of between 290 to 6000, a hydroxyl functionality between 15 to 600, and at least one carboxylic anhydride group. Specifically, the polycaprolactone urethane derivative can present a cross-linking configuration.
Bastioli et al. in U.S. Pat. No. 5,412,005 discloses a bioresorbable polymer composition that contains a starch-based component and a polymeric component. The polymeric component comprises polymer of hydroxyacids or mixtures thereof with polymers derived from ethylenically unsaturated monomers, such as PVA and EVA.
Neuenschwander et al in U.S. Pat. No. 5,665,831 disclose biocompatible block copolymers containing two distinct copolymer blocks. The block copolymers comprise the reaction product of α,ω-dihydroxypolyesters acid (or 3-hydroxyvaleric acid reacted) with ethylene glycol, or α,ω-dihydroxypolyesters with diisocyanate, diacid hilide, or phosgene. The biocompatible block copolymers exhibit bioresorbable properties and are suitable for implant materials.
Cohn et al. in U.S. Pat. No. 6,211,249 disclose an AB diblock comprising polyester polyether block copolymers, in which A block is derived from a polyester monomer, and B block is a polyalkylene oxide moiety with terminal non-reactive functional groups such as alkyl aryl, or aralkyl. The polyester polyether block copolymer has been applied to surgical operation to prevent adhesion.
Young Ha Kim in U.S. Pat. No. 6,476,156 discloses a process for preparing a bioresorbable triblock copolymer, comprising polyethyleneglycol/polylactide (or polyglycolide or polycaprolactone)/polyethyleneglycol triblock copolymers. The process thereof comprises the step of synthesizing a polylactide (or polyglycolide or polycaprolactone) having hydroxy groups at both ends, and a step of coupling the polylactide with polyethyleneglycol having acylhalide group of a high reactivity at one of its ends. Due to superior biocompatibility, the triblock copolymer is suitable for serving as a biomaterial for tissue engineering or as a polymeric carrier for drug release.
Kim et al. in U.S. Pat. No. 6,770,717 disclose a sequentially ordered bioresorbable lactide (or glycolide or lactide/glycolide)/epsilon-caprolactone multi-block copolymer having proper degradation properties and enhanced mechanical properties such as flexibility and elasticity.
Lee et al. (journal of control release, vol. 73, 315-327, 2001) disclose a process for preparing polyethyleneglycol/polycaprolactone diblock copolymer, with hexamethylene diisocyanate (HDI) as a coupling agent.
Cohn et al. (Biomaterials, 26, p. 2297-2305, 2005) disclose a triblock copolymer with a PLA-PCL-PLA structure (PLA: poly L-lactide; PCL: polycaprolactone), exhibiting superior flexibility. Specifically, the mechanical strength of the triblock copolymer can be adjusted by modifying the molecular weight of PLA.
The biodegradation period and mechanical properties of a bioresorbable polymer are key features in its utilization. There is still a need to develop a novel bioresorbable polymer with superior mechanical properties and modifiable biodegradation period.
The above references do not disclose or teach how to improve the mechanical strength and biodegradability of the polyester material. For example, due to the long biodegradation period of more than three years, the application of the polycaprolactone has been limited. Moreover, conventional polyester materials have high stiffness and are not suitable to serve as implant fixation devices used in human body. Therefore, the embodiments of the invention provided biodegradable materials by copolymerizing polyesters with different molecular weight. The obtained polyester polymer has modifiable biodegradation period and sufficient flexibility and elasticity.